DESCRIPTION: (Applicant's Description) The candidate, Dr. Timothy Lash, has been committed to cancer research since the beginning of his career. He studied molecular biology, including tumor biology, as an undergraduate at the Massachusetts Institute of Technology. Upon graduating, he worked as a consultant in environmental health on projects that required dose-response assessment of environmental and occupational carcinogens. Simultaneously, he completed a Masters of Public Health and the coursework for a Doctorate of Science in Epidemiology at the Boston University School of Public Health. The curricula for these degrees included many courses directly relevant to cancer prevention and control. He has worked on research projects involving breast cancer etiology, therapy, and side-effects of therapy under the direction of the proposed mentor (Dr. Rebecca Silliman) and the proposed co-mentor (Dr. Ann Aschengrau). Dr. Lash is currently an Assistant Professor of Epidemiology at the Boston University School of Public Health. He spends 75 percent of his effort on research projects directly relevant to the proposed research plan. For example, he is the project director on a study of adjuvant tamoxifen therapy in old age. Dr. Silliman is the Principal Investigator of the project, which will provide the cohort of breast cancer patients eligible for the second proposed study. Dr. Lash also works with Dr. Aschengrau, the proposed co-mentor, on analyses of the effect of active and passive smoking on breast cancer occurrence. The most recent case-control data set in which these analyses have been performed will provide the subjects eligible for the first proposed study. The environment at the Boston University Medical Center is ideally suited for accomplishing the career development goals of this application. The research plan proposes two studies of the interaction between tobacco smoke and NAT2 or COMT genetic polymorphisms. The association between tobacco smoke and breast cancer risk is complicated. It has been hypothesized that tobacco smoke exposure may both cause and prevent breast cancer, depending on the timing of exposure relative to reproductive milestones. The interaction with tobacco smoke exposure with the gene polymorphisms will allow tests of these hypotheses. The first study would collect buccal swabs from eligible participants of the second Cape Cod case-control study (Dr. Aschengrau was PI). Existing interview information would be combined with the polymorphism data extracted from the swabs to assess the interaction between the polymorphisms and tobacco smoke subgroups under a biologically based etiologic model of breast carcinogenesis. The second study would collect buccal swabs from participants in the study of adjuvant tamoxifen therapy (Dr. Silliman PI). A similar analytic plan would be conducted, but with a case-only design.